Herpes Virus Alters Cell Nuclei to Accelerate Replication, Study Finds
Herpes simplex virus (HSV-1) employs a clever tactic to speed up its replication within human cells: it partially liquefies the tightly packed interior of the cell nucleus. This groundbreaking discovery, led by researchers at NYU Langone Health, sheds light on how viruses overcome a fundamental barrier to infection and could pave the way for recent antiviral strategies.
The Nucleus: A Fortress for DNA, a Challenge for Viruses
The nucleus of each human cell serves as the control center, housing the genetic material (DNA) organized within a complex structure. This structure, known as chromatin, is densely packed to protect the DNA and regulate gene expression. While essential for cellular function, this density presents a challenge for viruses like HSV-1, which need access to the cellular machinery to replicate.
ICP4: The Key to Nuclear Fluidization
The NYU Langone Health study, published in Molecular Cell on March 5, 2026, identified a viral protein called infected cell protein 4 (ICP4) as the key player in this process. ICP4 works by attaching to proteins involved in chromatin remodeling, causing the DNA to unwind without initiating transcription. This unwinding loosens the nuclear interior, creating a more fluid environment.
How Fluidization Aids Viral Replication
Viruses require space to build “condensates”—dense droplets that concentrate molecules and serve as temporary factories for mass-producing new viral particles. By fluidizing the nucleus, HSV-1 creates more room for these condensates to form and grow, ultimately accelerating viral replication. Researchers found that blocking ICP4’s ability to fluidize the nuclear compartment resulted in a fourfold decrease in the production of new viral copies.
Visualizing Nuclear Changes
To visualize these changes, the research team engineered cells to produce glowing protein nanoparticles called nucGEMs. By tracking the movement of these particles, they observed a significant increase in motion within the nucleus when cells were infected with HSV-1, confirming the fluidization effect.
Implications for Antiviral Development
“The physical state of the nucleus is a fundamental barrier that this virus must overcome to multiply,” explained Dr. Liam J. Holt, PhD, a professor in the Department of Biochemistry and Molecular Pharmacology at NYU Grossman School of Medicine. “Viruses are masters at manipulating cells, and by studying their tricks, we uncover fundamental rules of biology.”
Researchers are now focused on understanding the precise mechanism by which ICP4 fluidizes the nucleus, with the goal of identifying new targets for antiviral therapies. Dr. Nora Herzog, PhD, a postdoctoral fellow at Universitat de València Parc Cientific, added, “We will also be looking to notice if this mechanism is used by other viruses that replicate in the nucleus, from double-stranded DNA viruses including the agent responsible for shingles to RNA viruses like influenza virus to retroviruses like HIV.”
Prevalence of HSV-1
According to a 2025 estimate, approximately 64 percent of adults worldwide have been infected with HSV-1, although many remain asymptomatic. NYU Langone Health notes this high prevalence underscores the importance of understanding viral replication mechanisms.
This research was supported by grants from the National Institutes of Health (NIH) (GM132447, AI176335, AI170583, GM056927, and AI073898), the National Science Foundation (NSF) (MCB-2145083), and the Hypothesis Fund.